Manipulation of nervous systems by electric fields

ABSTRACT

Apparatus and method for manipulating the nervous system of a subject through afferent nerves, modulated by an externally applied weak electric field. The field frequency is to be chosen such that the modulation causes excitation of a sensory resonance. The resonances found so far include one near 1/2 Hz which affects the autonomic nervous system, and a resonance near 2.4 Hz that causes slowing of certain cortical processes. Excitation of the 1/2 Hz autonomic resonance causes relaxation, sleepiness, ptosis of the eyelids, or sexual excitement, depending on the precise frequency used. The weak electric field for causing the excitation is applied to skin areas away from the head of the subject, such as to avoid substantial polarization current densities in the brain. Very weak fields suffice for bringing about the physiological effects mentioned. This makes it possible to excite sensory resonances with compact battery powered devices that have a very low current consumption. The method and apparatus can be used by the general public as an aid to relaxation, sleep, or sexual arousal, and clinically for the control and perhaps the treatment of tremors and seizures, and disorders of the autonomic nervous system, such as panic attacks.

Division of Ser. No. 08/788582, Jan. 24, 1997, now U.S. Pat. No.5,782,874, Jul. 21, 1998, which is a continuation-in-part of Ser. No.08/447394, May 23, 1995, abandoned, which is a continuation of Ser. No.08/068748, May 28, 1993, abandoned.

BACKGROUND OF THE INVENTION

The invention relates to electrical neurostimulation, wherein electriccurrents are passed to the brain, the spinal cord, an organ, orperipheral nerves 1-3!. Such stimulation has been used with variousdegrees of success for anesthesia, induction of relaxation and sleep, aswell for the treatment of pain, intractable epilepsy, behavioraldisorders, movement disorders, and cardiac arrythmia. The electriccurrent is usually delivered by contact electrodes i.e., electrodes thatare in Ohmic contact with the biological tissue. An exception is thecapacitor electrode of Guyton and Hambrecht 4!, which consists of animplanted porous tantalum disc with a thin insulating coating oftantalum pentoxide. After implantation, the pores fill withextracellular fluid and thus present a large capacitive interface to thefluid. The electrode is capable of delivering sizable currents to tissuewithout causing accumulation of electrochemical byproducts. Mauro 5! hasproposed another capacitor electrode in which one of the "plates" isformed by an electrolyte that is in Ohmic contact with the tissue, via athin tube. In both these cases the capacitance employed is large, suchas to pass currents of a magnitude and duration large enough to causefiring of the nerves, as expressed by the strength-duration curve withtypical times of 0.1 ms and currents of the order of 1 mA 6,7!. Thenerves fire as a result of substantial depolarization of the nervemembrane by the applied electric current, a process here calledclassical nerve stimulation.

An area of neurostimulation that has attracted much attention is theinduction of relaxation and sleep. One method, called Cranial ElectricStimulation (CES) involves passing an alternating current through thebrain via contact electrodes attached to the head or held in the mouth.With properly chosen strength and frequency, these currents may exciteor support brain waves that accompany deep sleep. The method has beenexplored extensively in the Former Soviet Union, under the name"Electrosleep".

A commercially available device is the Japanese "Sleepy" 8!, whichgenerates for one hour square pulses of 4 V and 0.2 ms duration, with afrequency that sweeps from 14 to 0 Hz, every 3 minutes. The devicerequires contact electrodes placed on the head. Other commercial CESdevices 9! are Alpha Stim, Mindman, and Endo Stim, which all requirecontact electrodes attached to the head.

Electric currents in biological tissue may also be induced by anelectric field that is generated in the space outside the subject. Theexternal electric field is set up by applying an electric potentialbetween field electrodes that do not have Ohmic contact with the tissue.Of course the arrangement may be seen as a form of capacitive coupling,but the capacitances are very much smaller than in Mauro 5! or Guytonand Hambrecht 4!. There is also an important practical difference, inthat no bodily contact with any part of the apparatus is required forthe electric field application by the field electrodes.

A neurological effect of external electric fields has been mentioned byNorbert Wiener 10!, in discussing the bunching of brain waves throughnonlinear interactions. The electric field was arranged to provide "adirect electrical driving of the brain" 10!. Wiener describes the fieldas set up by a 10 Hz alternating voltage of 400 V applied in a roombetween ceiling and ground.

Brennan 11! describes an apparatus for alleviating disruptions incircadian rythms of a mammal, in which an external alternating electricfield is applied across the head of a subject. The voltage applied tothe electrodes is specified as at least 100 V, and the peak-to-peakvalue of the electric field as at least 590 V/m in free air beforedeploying the electrodes across the head of the subject. The frequencyof the alternating electric field is in the range from 5 to 40 Hz.Brennan states that the method is aimed at subjecting at least part ofthe subject's brain to an alternating electric field, in the belief thatthis would stimulate an influx of Ca²⁺ ions into nerve endings, which inturn would "regulate and facilitate the release of neurotransmitters".Embodiments mentioned include electrodes arranged in a head cap, in abed, or mounted on the walls of a room. It should be noted that electricpolarization of the head causes the field strength in the narrow spacebetween electrode and skin to be about a factor h/2d larger than thefree-air field strength, h being; the distance between the electrodesand d the spacing between electrode and skin. For h=17 cm and d=5 mm thefactor comes to 17, so that with the specified free-air field of atleast 590 V/m the field in the gap between electrode and skin is atleast 10 KV/m peak to peak.

A device involving a field electrode as well as a contact electrode isthe "Graham Potentializer" mentioned in Ref. 9!. This relaxation deviceuses motion, light and sound as well as an external alternating electricfield applied predominantly to the head. The contact electrode is ametal bar in Ohmic contact with the bare feet of the subject; the fieldelectrode is a hemispherical metal headpiece placed several inches fromthe subject's head. According to the brief description in 9!, a signalless than 2 V at a frequency of 125 Hz is applied between the fieldelectrode and the contact electrode. In this configuration the contactelectrode supplies to the body the current for charging the capacitorformed by the field electrode and the apposing skin area. The resultingelectric field stands predominantly in the space between the head pieceand the scalp.

In the three external field methods mentioned, viz. Wiener 10!, Brennan11!, and Graham 9!, the electric field is applied to the head, therebysubjecting the brain to polarization currents. These currents runthrough the brain in a broad swath, with a distribution influenced bynonuniformities of conductivity and permittivity. The scale of thecurrent density can be conveniently expressed by the maximum value, overthe skin of the head, of its component perpendicular to the local skin.This scale is easily calculated for sinusoidal fields as the product ofradian frequency, permittivity, and maximum amplitude of the externalfield on the head. Using Brennan's 11! lowest frequency of 5 Hz, hisminimum required free-air field strength of 590 V/m, and the factor 17as estimated above to account for the polarization of the head by theapplied field, the scale of the polarization current density in thebrain comes to about 280 pA/cm². Without understanding the neurologicaleffects involved, it is prudent to avoid exposing the brain to currentdensities of such scale, and impose as a limit 1/4000 times the scalecalculated for Brennan's patent. Polarization current densities in thebrain with a scale in excess of 70 fA/cm² are henceforth consideredsubstantial.

It is the object of the present invention to obtain a method andapparatus for manipulating the nervous system by external electricfields without causing substantial polarization currents in the brain.

The use of electric fields raises concerns about possible healtheffects. Such concerns have been widely discussed in the media in regardto electric power lines and electric apparatus 12!. Answering thepertinent questions by objective research will take time, but meanwhilegovernments have been setting guidelines for safe limits on fieldstrengths. At present, the strictest limits of this sort are the SwedishMPRII guidelines. Magnetic fields are of no concern here, because thecurrents involved are so small. However, the electric field strengthymust be considered, since even at low voltages strong electric fieldscan result from electrodes placed close to the skin. For extremely lowfrequency fields, the MPRII guidelines limit the field strength to 25V/m in the frequency range from 5 Hz to 2 KHz. In the Brennan patent 11!the minimum field strength of 590 V/m violates the guidelines by afactor 23; when the polarization effects are accounted for, the factoris about 400.

It is a further object of the present invention to manipulate thenervous system by external electric fields that are in compliance withthe MPRII guidelines.

Brennan 11! stipulates voltages of at least 100 V, and as high as 600 Vfor his preferred embodiment. Generation of such voltages requires avoltage multiplier stage, if practical battery operation is desired.This increases the current drain and the size of the generator. Thelarge voltages also raise safety concerns.

It is yet a further object of the present invention to manipulate thenervous system by external electric fields, using low voltages that aregenerated by a small and safe battery-powered device with low currentconsumption.

SUMMARY

Experiments have shown that weak electric fields of frequency near 1/2Hz applied externally to the skin of a subject can cause relaxation,doziness, ptosis of the eyelids, or sexual excitement, depending on theprecise frequency used. In these experiments the electric field wasapplied predominantly to skin areas away from the head, thereby avoidingsubstantial polarization current densities in the brain. Apparently, theexternal electric field somehow influences somatosensory or visceralafferent nerves, which report the effect to the brain. Although themechanism whereby the field acts on the afferents is unknown, the effectmust take the form of a slight modulation of the firing patterns of thenerves, because the polarization current densities induced by the fieldare much too small to cause firing of the nerve. If the applied externalfield is periodic, so will be the modulation of the firing patterns ofaffected afferent fibers, and the brain is then exposed to an evokedperiodic signal input. Apparently, this signal input influences certainresonant neural circuits, the state of which has observableconsequences. Since the resonances are excited through somatosensory orvisceral afferents, they are here called "sensory resonances".

Besides the resonance near 1/2 Hz that affects the autonomic nervoussystem, we have also found a resonance near 2.4 Hz which slows certaincortical processes. For both resonances the external electric field onthe skin must lie in a certain range of values for the physiologicaleffects to occur. This "effective intensity window" can be determinedaccurately for the 2.4 Hz resonance, by measuring the time needed tocount silently backward from 100 to 70.

The effective intensity window depends on the number of afferentsmodulated by the field. This "bulk effect" is important for the properuse of the invention, and has therefore been explored in preliminaryexperiments. At the lower boundary of the window the external fieldstrengths are very small, down to 10 mV/m when a large skin area isexposed to the field. The fact that very small external field strengthssuffice for the excitation of sensory resonances through modulation ofafferents allows the use of small battery-powered electric fieldgenerators that can be used conveniently by the general public as an aidto relaxation, sleep, or sexual excitement, and clinically for thecontrol and perhaps a treatment of tremors and seizures, and disordersof the autonomic nervous system such as panic attacks.

Compliance of the devices with the MPRII guidelines on field limits inthe ELF and VLF frequency bands is easily achieved.

The field generators shown involve simple low voltage generators basedon 555 type timer chips, and field electrodes that are small enough tofit in a single small casing, such as a powder box.

Although the mechanism of electric field modulation is unknown,candidates for cutaneous receptors that may be susceptible to thismodulation are indicated.

DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a preferred embodiment, and shows the deployment of fieldelectrodes external to the body of the subject.

FIG. 2 illustrates the electric field generated between the fieldelectrodes and the subject's body.

FIG. 3 shows an embodiment which generates an electric field thatfluctuates as a rounded square wave, and includes an automatic shutoff.

FIG. 4 shows an embodiment which generates an electric field thatfluctuates as a rounded square wave, and which includes an automaticfrequency shift and automatic shutoff.

FIG. 5 shows an embodiment which generates an electric field thatfluctuates as a rounded square wave with a chaotic time dependence, andwhich includes an automatic shutoff.

FIG. 6 shows the map of time intervals between consecutive transitionsof the chaotic square wave generated by the circuit of FIG. 5.

FIG. 7 shows an embodiment in which the field electrodes and generatorare contained in a powder box.

FIG. 8 shows schematically a shielded pair of electrodes.

FIG. 9 shows the effective intensity window for currents passed bycontact electrodes to the skin overlying the vagus nerve.

FIG. 10 shows the effective intensity window for large skin areaexposure to the field from a small electrode pair placed some distancefrom the subject.

FIG. 11 is a replot of the data of FIG. 10, to serve in a comparisonwith the data of FIGS. 12 and 13.

FIG. 12 shows the effective intensity window for an experiment using ashielded electrode pair placed on the thighs.

FIG. 13 shows the effective intensity window for an experiment using ashielded electrode pair placed on the finger tips.

DETAILED DESCRIPTION

The invention is based on the discovery, made in our laboratory, thatneurological effects can be induced by weak external electric fields ofa precisely tuned frequency near 1/2 Hz, when applied to skin areas awayfrom the head. The observed effects include ptosis of the eyelids,relaxation, drowziness, the feeling of pressure at a centered spot onthe lower edge of the brow, seeing moving patterns of dark purple andgreenish yellow with the eyes closed, a tonic smile, a tense feeling inthe stomach, and sexual excitement, depending on the precise frequencyused. These effects were observed initially for external field strengthsin the range from 1 to 25 V/m, but recent experiments have shown effectswith much weaker and stronger fields.

In these experiments the polarization current densities produced inbiological tissue by the applied external electric field are much toosmall to cause classical nerve stimulation, yet a central nervous systemresponse is evoked. Experiments have shown that signal pathways otherthan afferent nerves are not involved. It follows that weak externalelectric fields can evoke some sort of signal that is carried byafferent nerves. Since classical nerve stimulation cannot occur, thesesignals must have the form of a modulation of spontaneous firingpatterns. The simplest such modulation is frequency modulation (fm), butmore subtle modulation modes 26! may be involved. For simplicity ofdescription however, we will refer to the modulation as fm. In ourexperiments the modulation depth is very small, but for fieldfrequencies close to the resonance frequency of receptive neuralcircuits the weak incoming fm signal can evidently cause excitation ofthe resonance with observable consequences. Since the applied fields aremuch too weak to cause nerves to fire, the sensory and visceralreceptors and afferents susceptable to modulation must exhibitspontaneous firing.

Since the resonances are excited through somatosensory or visceralafferent nerves, they are here called sensory resonances. The sensoryresonance near 1/2 Hz involves the autonomic nervous system and istherefore sometimes called the 1/2 Hz autonomic resonance.

Exploitation of sensory resonances and reliance on modulation ofspontaneous firing patterns rather than classical nerve stimulationmakes it possible to manipulate the nervous system with very smallelectric fields, induced by low voltages. Moreover, employing thenatural pathways of afferent nerves into the brain allows application ofthe field to skin areas away from the head. The invention thereby meetsthe stated objects of providing manipulation of the nervous systemwithout causing substantial polarization current densities in the brain,compliance with MPRII field limits, and use of a low voltage batterypowered generator with small current assumption.

The invention provides a method and apparatus for maniplating thenervous system of human subjects. Such manipulation comprises relaxationand the induction of sleep or arousal, as well as the control andperhaps a treatment of tremors, seizures, and disorders resulting from amalfunction of the autonomic nervous system, such as panic attacks.

In the early experiments the excitation of the sensory resonanceoccurred through the modulation of cutaneous nerves by the appliedelectric field. In later experiments with larger field strengths,similar physiological effects have been obtained by applying the fieldto the skin overlying the vagus nerve or the sciatic nerve. It appearsthat excitation of sensory resonances can be achieved through anyafferent pathway, provided that it is broad.

A new sensory resonance has been found at 2.4 Hz, characterized by apronounced increase in the time needed for silently counting backwardfrom 100 to 70. Prolonged exposure to the excitation was found to have asleep-inducing and dizzying effect. Recent experimental results will bediscussed towards the end of the specification.

The equipment suitable for the generation of the weak electric fieldsused for the modulation of afferent nerves consists of field electrodesand a voltage generator. The field electrodes can be conductive foils,wires or meshes that may optionally be covered on one or both sides withan insulating layer. The field electrodes are to be electricallyconnected to the generator, but insulated from the subject. The voltagegenerator is to produce a low flucuating voltage. Harmonic content needsto be considered for compliance with MPRII guidelines, if the amplitudeof the field applied to the skin is large. An automatic shutoff can beprovided, such as to limit the duration of the field administration.

It has been found that a single half hour application of the field isusually sufficient to induce sleep, if the frequency is tuned correctlyfor the individual to a frequency near 1/2 Hz. Shorter application timesare typically sufficient for inducing relaxation.

A preferred embodiment is shown in FIG. 1, where the voltage generator1, labelled as GEN, is connected to the field electrodes 2 by wires 3;the field electrodes 2 are positioned away from the subject 4. Thevoltage generator may be tuned manually by the user with the tuningcontrol 21. As an option, sheet conductors 43 and 43' such as aluminumfoils may be placed near the subject in order to diminish interferencefrom a 60 Hz or 50 Hz house field, to be discussed. Referring to FIG. 2,application of a voltage between the field electrodes 2 produces anelectric field 5 between field electrodes 2 and the subject 4, for thecase that the sheet conductors 43 and 43' of FIG. 1 are absent. Thefield is applied predominantly to skin areas away from the head of thesubject; in the setup of FIG. 1 these areas comprise skin area 36 on thehips, buttocks, and lower back, and skin area 36' on the back side ofthe thighs and knees.

A suitable voltage generator, built around two RC timers, is shown inFIG. 3. Timer 6 (Intersil ICM7555) is hooked up for astable operation;it produces a square wave voltage with a frequency determined byresistor 7 and capacitor 8. The square wave voltage at the output 9drives the LED 10, and appears at one of the output terminals 11, aftervoltage division by potentiometer 12. The other output terminal isconnected to an intermediate voltage produced by the resistors 13 and14. As a result, the voltage between the output terminals 11 alternatesbetween positive and negative values. Automatic shutoff of the voltagethat powers the timer, at point 15, is provided by a second timer 16(Intersil ICM7555), hooked up for monostable operation. The shutoffoccurs after a time interval determined by resistor 17 and capacitor 18.Timer 16 is powered by a 3 V battery 19, controlled by the switch 20.The output terminals 11 are connected to the field electrodes 2 byconductors 3. The resistors 13 and 14 not only serve as a voltagedivider that gives the intermediate voltage needed to produce analternating square wave, but these resistors also provide currentlimitation. A further decrease of the currents induced in the subject iscaused by the output capacitor 22, in a manner to be discussed. There isthe option of including a switch 44 in the output circuit, in order toprevent polarization of the electrode assembly by a 60 Hz or 50 Hz housefield when the device is inactive, to be discussed.

A time variation of frequency may be accomplished by manipulating thecontrol voltage of one section of a dual timer with the output of theother section. An embodiment for this type of operation is shown in FIG.4. The dual timer 23 (Intersil ICM7556) is powered at point 24 byvoltage from the output 15 of timer 16 (Intersil ICM7555), which servesas an automatic shutoff after a time interval determined by resistor 17and capacitor 18. The timer operation is started by closing switch 20.The voltage at output 25 of the dual timer 23 drives the LED 10, and isapplied, via the variable resistor 12, to one of the outputs 11 of thevoltage generator. Resistors 14 and 13 serve to provide an intermediatevoltage at the other output terminal 11, such as to result in apotential difference between the output terminals that alternatesbetween positive and negative values of substantially equal magnitudes.The frequency of the square wave voltage at point 25 depends on resistor7 and capacitor 8. The frequency is also influenced by the controlvoltage applied to the timer. A frequency upshift can be obtained byapplying the output of the second section of the dual timer 23 to thecontrol voltage pin of the first timer section, via resistor 26. Thissecond timer section is hooked up for monostable operation. The outputterminals 11 are connected by conductors 3 to the field electrodes 2,which are pieces of aluminum foil, covered by insulating tape on bothsides.

The automatic shutoff and time variation of the frequency are examplesof automatic control of the fluctuating voltage generated by thegenerator.

Low frequencies can be monitored with an LED 10 of FIG. 3. The LEDblinks on an off with the square wave, and doubles as a power indicator.The frequency can be determined by reading a clock and counting LEDlight pulses. For higher frequencies a monitoring LED can still be used,if it is driven by a wave obtained by frequency division of thegenerator output wave .

The voltage generators discussed above have oscillators of the RC type,but other types of low-voltage oscillators can be used as well. Forinstance, the voltage generator can be built as a digital device, inwhich a square wave output is derived from a clock signal by means offrequency division. Chaotic signals, time variation of frequency,programmed frequency sequences, automatic turn on and shutdown,frequency adjustment, and frequency monitoring may also be accomplisheddigitally. A computer that runs a simple timing program can be used forthe generation of all sorts of square waves that can be made availableat a computer port. An economic and compact version of such arrangementis provided by the Basic Stamp 30!, which has an onboard EEPROM that canbe programmed for the automatic control of the fluctuating voltagegenerated, such as to provide desired on/off times, frequency schedules,or chaotic waves. In the interest of controlling polarization currentpeaks or complying with MPRII guidelines, the square waves can berounded by RC circuits, and further smoothed by integration andfiltering. In this manner, near sinusoidal output can be achieved. Suchoutput can also be obtained with a digital sine wave generator based ona walking-ring counter 31!, or with a waveform generator chip such asthe Intersil ICL8038. Analog circuits for tunable sine wave generatorsbased on LC oscillators with passive inductance and capacitance are notpractical because of the very large component parameter values requiredat the low frequencies involved. Large inductances can be produced by acompact active stage, or one can use two separate RC phase shiftcircuits connected in a loop with an amplitude limiter 32!. Tuning maybe done with a single potentiometer.

Applications are envisioned in which the field electrodes are drivenwith a fluctuating voltage that is chaotic. Such a voltage is heredefined as a signal for which the times of zero crossings or peaks, orboth, form a pseudo-random sequence. A simple example is provided by asquare wave for which the transition time intervals form a pseudo-randomsequence, within upper and lower limits. The brain is adaptive, but thechaotic transitions are difficult to learn and anticipate, and thereforea field with a slightly chaotic square wave can thwart habituation. Asensory resonance can still be excited by such a wave, if the averagefrequency of the wave is close to the resonant frequency. The chaoticwave can also be used to upset pathological oscillatory modes in neuralcircuitry, such as to control tremors in Parkinson patients.

An embodiment which involves a chaotic square wave electric field isshown in FIG. 5. The dual timer 23 (Intersil ICM7556) is powered, atpoint 24, by the output 15 of timer 16 (Intersil ICM7555), hooked up formonostable operation, such as to provide automatic shutoff after a timedetermined by resistor 17 and and capacitor 18. Operation of timer 16 isstarted by closing switch 20. Both sections of the dual timer 23 arehooked up for bistable operation, with slightly different RC times. Thevoltage at output 25 of the first timer section is used to drive the LED10; after voltage division by the variable resistor 12, the voltage isapplied to one of the outputs 11. The other output 11 is an intermediatevoltage from the voltage divider formed by resistors 14 and 13. Theouputs 11 are connected to the field electrodes 2 through conductors 3.The RC time of the first timer section is determined by resistor 7 andcapacitor 8. The RC time of the second timer section is determined byresistor 27 and capacitor 28. The two timer sections are coupled byconnecting their outputs crosswise to the control voltage pins, viaresistors 29 and 30, with capacitors 31 and 32 to ground. For a properrange of component values, easily found by trial and error, the squarewave output of each of the timer sections is chaotic.

An example for chaotic output is shown in FIG. 6, where the pointsplotted correspond to transitions (edges) of the square wave. Abscissa33 and ordinates 34 of a plotted point are time durations betweenconsecutive transitions of the square wave output; for any transition,the abscissa is the time to the preceding transition, and the ordinateis the time to the next transition. Starting with transition 35,consecutive transitions are found by following the straight lines shown.The transition times follow a pseudo random sequence, with some orderprovided by the oval attractor. The results shown in FIG. 6 weremeasured for the device of FIG. 5, with the following component values:R₇ =1.22 MΩ, R₂₇ =1.10 MΩ, R₂₉ =440 KΩ, R₃₀ =700 KΩ, C₈ =0.68 μf, C₂₈=1.0 μf, C₃₁ =4.7 μf, and C₃₂ =4.7 μf. In the above list, R_(i) is theresistance of component i in FIG. 5, and C_(j) is the capacitance ofcomponent j.

Tests with a subject who is not a Parkinson patient, but who has a handtremor of another origin, have shown good control of the tremor by asquare wave electric field with the chaotic time dependence shown inFIG. 6. The device of FIG. 5 was used in these tests, with electrodesplaced vertically on two opposite vertical sides of the seat cushion ofan easy chair.

In the present invention, the external field is applied predominantly tocertain selected areas of the skin of the subject, such as the areas as36 and 36' in FIG. 2. Areas of predominant field application are heredefined to consist of all points of the skin at which the absolute valueof the resultant field strength is at least twice the average over theskin. The resultant field includes the field produced by polarizationcharges on the skin of the subject. The resultant field is perpendicularto the skin when the polarization keeps up with changes in the appliedfield, as is the case for the low frequencies involved, if sharptransitions are avoided.

Of convenience in social settings is an embodiment in which the twofield electrodes and the signal generator are contained in a singlecasing such as a small box, purse, powder box, or wallet. An embodimentis shown in FIG. 7, where the generator 1' with tuning control 21' isplaced inside a powder box casing 45 with hinge 49. The field electrodes2 and 2' are contained in the casing 45. The field electrodes 2 areconnected to the generator 1' by conductors 3. For brevity, fieldelectrodes mounted on the outside surface of a casing are considered ascontained in the casing.

The peak-to-peak variation of the output voltage of the voltagegenerators discussed above cannot exceed 16 V, because of supply voltagelimitations for the CMOS timer chip. However, much lower output voltagessuffice for most applications. An output voltage of 2.4 V peak to peakis adequate for the setup of FIG. 1. Such an output voltage is providedby the signal generators of FIGS. 3 and 4, when powered by a 3 Vbattery. Such small voltages suffice even for embodiments in which thegenerator and field electrodes are mounted in a single small casing, inspite of the small area available for the electrodes.

An electric field outside the body of the subject is called an externalelectric field.

In applications of modulation of cutaneous nerves by an externalelectric field there is usually also present a 60 Hz or 50 Hz housefield, i.e., an electric field emanating from house wiring, electricapparatus and electric power lines. House fields can have considerablestrength; Becker and Marino 15, table 10.4! list the electric field, at1 ft distance from an electric blanket, broiler, refrigerator, foodmixer, hairdryer, and color TV, respectively as 250, 130, 60, 50, 40,and 30 V/m. The electric field 1 ft away from a light bulb is listed as2 V/m. The house field may cause inadvertent modulation of cutaneousnerves. In distinction with this inadvertent modulation, there is thepurposeful modulation which is the subject of the present invention. Thehouse field intensities mentioned above suggest that the house field mayinterfere with the purposeful modulation. The interference can bediminished by reducing the strength of the house field incident on thesubject. This may be done by placing near the subject a sheet conductororiented roughly parallel with the local house field. An example isshown in FIG. 1, where a sheet conductor in the form of aluminum foils43 is placed against the underside of the bed, and a continuation 43' ofthe aluminum foil covers the back of the headboard. Thehouse-field-diminishing effect of a properly placed and oriented sheetconductor can be readily understood as due to electric polarization ofthe sheet conductor by the house field.

There further is concern about the effect of house field inducedelectric polarization of the electrode assembly, that may occur at timeswhen no external electric field is being generated by the apparatus,although the field electrodes are electrically connected through thedevice. This state occurs during most of the night, if the apparatus ofFIGS. 3 or 4 is used as a sleeping aid with permanently placed fieldelectrodes, after the automatic shutoff has cut the power to theoscillator. Of concern is the circuit comprised of the two fieldelectrodes, their connections to the signal generator, and pertinentoutput circuitry in the signal generator. Referring to FIG. 3, it isseen that this circuit includes the capacitor 22 and part of thepotentiometer 12. The house field generally induces polarizationcurrents in this circuit. The resulting polarization charges on thefield electrodes induce an electric field with a nonuniformity scalecomparable to the electrode spacing. This 60 Hz field may causemodulation of the same afferent nerves as those involved in thepurposeful modulation by the apparatus field. The inadvertent modulationmay cause weak fm signals of 60 Hz frequency in receptive neuralcircuitry, and the signals may be so weak as to sneak bynuisance-guarding circuitry. The unwanted signals may be diminished byusing the house-field-diminishing sheet conductor described above.Alternatively, or in addition, polarization of the electrode assembly bythe house field may be prevented by breaking the electric connectionbetween the field electrodes by means of a switch (44 in FIG. 3) in oneof the output leads of the signal generator. This switch may be gangedwith the power switch.

The external electric field must be predominantly applied to skinregions away (at least 10 cm) from the head of the subject. Furthermore,substantial polarization current densities in the subject's brain mustbe avoided. The scale of these current densities is expressed here asthe product of permittivity, radian frequency of the field, and maximumexternal electric field amplitude on the head; this product should notexceed 70 fA/cm². Satisfying this condition and that of predominantfield application to skin areas away from the head requires calculationof external field strengths on the subject's skin, for the fieldelectrode configuration and deployment considered. This can be donealong the following lines.

First, the electric field produced by a field electrode at distance r isgiven by the well known Coulomb formula, for r considerably larger thanthe electrode dimensions. For elongated electrodes, the two-dimensionalCoulomb formula can be used for intermediate distances that are largecompared to a significant dimension of the cross section but smallcompared to the electrode length. The presence of the subject can beaccounted for by the well-known method of images 27!. The field producedby a field electrode in its immediate vincinity can be calculated withsimple models that are appropriate to the situation at hand, and arewell known to those skilled in the art. Of course, these calculationsneed only be approximate or furnish reliable upper bounds of the fieldstrength considered. Field calculations will be shown here for severalfield electrode configurations and settings of practical interest.

Presently, the experiments that underlie the invention will bediscussed. The experiment setup used was much like the one shown in FIG.1, with variations as to the skin area of predominant field application.The voltage applied between the field electrodes was usually a squarewave with a frequency that can be manually tuned from 0.1 to 3 Hz, byadjusting the tuning control 21 on the generator 1 of FIG. 1; thevoltage of the square wave was about 3 V. Frequencies at which aphysiological effect occurs were found by manual frequency scanning. Weneeded a way to tell whether the nervous system of the subject was beingaffected by the external electric field. Invasive procedures were ruledout. Extensive EEG measurements were done on the scalp over appropriatepoints on the postcentral gyrus, using the method of averaging over manysweeps, in order to recover evoked potentials 13!. No evoked potentialsshowed up, even after averaging over 8000 sweeps, which brought thesensitivity to 100 nV. This showed that if anything is going on with thecutaneous nerves in the skin areas exposed to the field, it is notclassical nerve stimulation. It was noticed that, at frequencies ofabout 1/2 Hz, the subject became drowsy and the EEG eventually showedincreased amplitudes of slow waves, as judged by the signal waveform.The experiments need to be repeated, using hardware or software thatprovides for fast spectral analysis. Lacking this equipment, we lookedfor another indicator and found one in the form of ptosis of theeyelids.

When voluntary control of the eyelids is relinquished, the eyelidposition is determined by the state of the autonomic nervous system 13!.There are two ways in which this indicator may be used. In the first thesubject simply relaxes control over the eyelids, and makes no effort tocorrect for any drooping. The more sensitive second method requires thesubject to first close the eyes about half way. While holding thiseyelid position, the subject rolls the eyes upward, while giving upvoluntary control of the eyelids. With the eyeballs turned up, ptosiswill decrease the amount of light admitted into the eyes, and with fullptosis the light is completely cut off. The second method is verysensitive because the pressure exerted on the eyeballs by partiallyclosed eyelids increases parasympathetic activity. As a result theeyelid equilibrium position becomes labile, as characterized by a slightflutter. The labile state is sensitive to small shifts in the activitiesof the sympathetic and parasympathetic nervous system. The method worksbest when the subject is lying flat on the back and is viewing a blankwall that is dimly to moderately illuminated.

With this arrangement maximum ptosis occurred at a frequency near 1/2Hz, with external electric field amplitudes on the skin ranging from 1V/m to 25 V/m, where field amplitude is defined as half the peak-to-peakvariation of the field strength. Immediately after onset, the ptosisfrequency, defined as the frequency for maximum ptosis, slowly decreasesuntil a steady frequency is reached in 5 to 10 minutes. It is believedthat this is due to changes in the chemical environment of theresonating neural circuitry, caused by changes in the concentration ofneurotransmitters or hormones that accompany or result from theresonance or from the subsequent shift in the autonomic nervous systemstate. The effect is here called "chemical detuning" of the ptosisfrequency. The slow shift of ptosis frequency initially is so large thatptosis is lost if the frequency is not adjusted. The ptosis isaccompanied by a state of deep relaxation, and a slight dull pressure ata spot about 1 cm above the point midway between the eyes.

As directed demonstrated by the ptosis experiments, the method of thepresent invention can be used for inducing relaxation in a subject. Infurther experiments with the device of FIG. 3 it has been found that, ina narrow range of frequencies around the ptosis frequency, the subjectbecame very relaxed after a few minutes of field application, using peakfield strengths on the subject's skin of about 1 V/m. The field wasinduced by field electrodes placed on the sides of the seat cushion ofan easy chair. The ptosis frequency is higher in the evening than in themorning, just after awakening. For the subject tested, the eveningptosis frequency was 0.512 Hz at the onset, slowly shifting downwards to0.465 Hz in about 10 minutes. Other autonomic responses can be obtainedas well; tuning to a frequency of 0.540 Hz brings forth a tonic smile,provided that the subject gives up voluntary control of the facialmuscles involved, so that the smile is controlled by the autonomicnervous system. Relaxation was experienced in the frequency range from11% below to 4% above ptosis frequency. In the morning, the ptosisfrequency at the onset was 0.490 Hz initially, shifting downwards to0.460 Hz in about 7 minutes.

The method can also be used for the induction of sleep. Long-term testsrunning for about 400 nights were conducted on a subject who had troublesleeping due to prolonged severe situational stress. In these tests, anexternal electric field was set up by applying a square-wave voltage of20 V peak to peak between two field electrodes placed directlyunderneath the bed sheet on both sides of the hips. Good results wereobtained with frequencies of about 1/2 Hz. More recently, the device ofFIG. 4 with a 3 V battery has been used successfully by the same subjectfor about 300 nights, under the same stressful conditions. Among thevarious electrode positions tried, the placement depicted in FIG. 1 wasfound to be most effective for inducing peaceful sleep. In thisconfiguration the field electrodes 2 are located directly under themattress, in the vertical mid plane through the longitudinal axis. Themaximum electric field amplitude on the subject's skin is estimated asabout 1 V/m. Two modes of operation were used. In the first mode, theunit was turned on at bedtime, at a frequency of 0.545 Hz, andthereafter left alone. After 15 minutes, the device automatically shiftsthe frequency upward by 3%, and turns off the oscillator after another15 minutes. The subject usually fell asleep before automatic shutoff hadoccurred. A second mode of operation involves initial tuning for ptosis,followed by manual tracking of the slowly downshifting ptosis frequency,using the tuning control 21 shown in FIG. 1. About 5 minutes after asteady ptosis frequency is reached, the device is shut off manually.Tracking the ptosis frequency during its downward shift brings anincreasingly deep state of relaxation and detachment. Sleep usuallyfollows shortly after the device is shut off manually.

In regard to electrode placement there is a fundamental neurologicaldifference between antisymmetric and symmetric excitation, in which theskin polarization is respectively antisymmetric and symmetric withrespect to the sagittal plane. In antisymmetric excitation, the weak fmsignals from the modulated afferents act antisymmetrically on the brain.As a consequence, resulting resonances in neural circuits exhibitantisymmetry in left and right hemispheres, and the corpus callosum is"caught in the middle". In symmetric excitation, resonant modes occursynchronously in both hemispheres, and the corpus callosum is lessinvolved, if at all. Experiments have shown that induction of sleepoccurs with both excitations, but the symmetric excitation gives asomewhat softer feeling.

At frequencies somewhat different from the ptosis frequency, sexualarousal has been observed. In a male subject 67 years of age, theincidence of morning erections increased considerably when a square wavevoltage was applied to field electrodes 2 placed as shown in FIG. 1, ata frequency of 0.563 Hz, and also, to a lesser extent, at a frequency of0.506 Hz. These frequencies were found by manual scanning the range fron0.1 to 3 Hz. The signal generator of FIG. 3 was used, powered by a 3 Vbattery. For frequencies near 0.55 Hz, rather intense sexual excitementlasting for up to an hour has been induced in a male subject 70 years ofage, by applying the external electric field predominantly to a skinarea that includes the perinaeum skin.

Cutaneous receptors are particularly dense in glabrous skin, such asfound on the palms of the hand, footsoles, areas of the genitals,nipples, areola, and lips. In the somatosensory map between areas ofskin, the thalamus, and sensory cortex, the representation of theseglabrous skin areas is greatly amplified. As a consequence, externalelectric field modulation of cutaneous nerves in glabrous skin isexpected to excert a particularly strong effect on the central nervoussystem. We feel that this should be avoided by the general public; theeffects are already ample when the field is applied predominantly toareas of the skin which are innervated sparsely, such as the thighs andthe back. In particular, the lips should not be exposed strongly to thefield, so that the areas of predominant application of the electricfield by the general public should be away (say, at least 10 cm) fromthe head. Another reason for such choice is the avoidance of substantialpolarization current densities in the brain, as discussed above.

Fixing experiment parameters except for the field strength, thedescribed physiological effects are observed only for field intensitiesin an interval, called here "the effective intensity window". Thisfeature of sensory resonances may be understood as due tonuisance-guarding neural circuitry that blocks impertinent repetitivesensory signals from higher processing. For the guarding circuitry tospring into action, the amplitude of the nuisance signal needs to exceeda certain threshold. This explains the upper boundary of the effectiveintensity window. The lower boundary of the window is due to thedetectibility threshold of the sensory signals.

There needs to be concern about kindling 13, 18! of epileptic seizuresin susceptable individuals. Kindling has traditionally involved thepassage of electric currents of the order of 0.1 mA directly to a partof the brain, such as the amygdala. Although in the present inventionsubstantial polarization current densities in the brain are avoided, aneffect similar to kindling might occur if critical neural circuits aresubjected to repeated sessions of periodic fm signals from somatosensoryor visceral afferents. To guard against such an effect, the frequency ofmodulation of afferents for use by the general public should be chosenaway from the frequencies involved in epileptic seizures. Frequenciesbelow 2 Hz appear to qualify in this regard.

The pathological oscillatory neural activity involved in epilepticseizures 13! is influenced by the chemical milieu of the neuralcircuitry involved, specifically through concentrations of GABA,glutamate, and aspartate 18!, and perhaps β-endorphin. Since excitationof the 1/2 Hz sensory resonance may cause a shift in some of theseneurotransmitter concentrations, the application of external electricfields may be useful for control and perhaps treatment of seizures. Forthis purpose, the patient wears compact field electrodes and agenerator, to be manually activated upon experiencing a seizureprecursor or aura. For patients with infrequent seizures, a small unitthat contains the field electrodes as well as the generator, in the formof a small box, wallet, purse, or powderbox, may be particularlysuitable.

The modulation of afferents by external electric fields may also be usedfor the control of tremors in Parkinson patients, by interfering withthe underlying pathological oscillatory activity. According to Ref. 14!,Scientific American of 1892 contains an article about controllingParkinson symptoms by means of a vibrating helmet placed on thepatient's head. For a 10 Hz vibration frequency, the subject is reportedto experience, within a few minutes, a general lassitude and a tendencyto sleep. Modulation of afferent nerves by a properly tuned periodicexternal electric field affords another and far less conspicuousexcitation method, which is expected to have a similar result. Themethod of upsetting pathalogical oscillatory activity by applying anexternal electric field for modulating afferent nerves in skin areasaway from the head may also be used for the control of seizures.

The method may be applied for the control of panic attacks, when theseinvolve an abnormally high activity of the sympathetic nervous system.The experiments on ptosis, relaxation, and sleep show that theapplication of alternating external electric fields can diminish theactivity of the sympathetic nervous system. The apparatus of FIG. 3 maybe used, tuned to a frequency just below ptosis, or, for severe cases,right at ptosis. In this application it is convenient to use a generatorand field electrodes mounted in a small single casing, such as a smallbox, wallet, purse, or the powder box of FIG. 7.

The question arises whether in the weak-field experiments discussedabove the observed physiological effects are perhaps due to mechanismsother than the response of afferent nerves to the applied field.Candidates for such alternate mechanisms are polarization currentsinduced in the brain, and currents carried along high-conductivity pathsprovided by the cerebrospinal fluid, blood, and lymph, and subsequentlydetected by receptors. These alternate mechanisms are ruled out byexperiments in which a sharply localized electric field is applied tothe dorsum of the feet. The usual array of physiological responses wasfound in these experiments. It is therefore concluded that for weakaplied electric fields the observed physiological effects are indeedinstigated by a response of afferent nerves to the external electricfield.

The manipulation of the nervous system by external electric fields tunedto a sensory resonance frequency is subject to habituation,sensitization, classical conditioning, and the placebo effect. Tominimize habituation in the use as a sleeping aid, the field should bepredominantly applied to a different skin area each night.Sensitization, the placebo effect, and positive classical conditioningenhance the efficacy of the method. Clinical trials can be designed suchthat the placebo effect does not contribute to the statistical mean.This is done by arranging the generator output to the field electrodesto be passed or blocked by computer, according to a pseudo-randomsequence with a seed that is changed from run to run, as determined forinstance by date and time. Whether the field was on or off is unknownuntil the run is complete and the response of the subject has beenentered into the computer. The arrangement is equivalent to a trullydouble-blind study.

The following considerations are important for proper design and use ofthe field generator, as well as for the planning and interpretation ofexperiments.

When an external electric field is applied to an isolated conductor,electric currents will flow that drive charges to the conductor surface.In steady state, these charges are distributed in such a way that thetotal electric field inside the conductor vanishes and the conductorsurface is equipotential. These surface charges and electric currentsare here called respectively "polarization charges" and "polarizationcurrents". Although mainly used in the context of dielectrics, thewording is proper for isolated conductors as well.

Since the human body is a good conductor of electricity, exposure of anisolated subject to an alternating external electric field will causepolarization currents to flow broadly through the subject's body. Thecurrents are of course accompanied by an ("internal") electric field,which turns out to be a very small fraction of the applied externalfield. In principle the polarization current and accompaning internalelectric field may act on receptors, axons, synapses, and dendrites. Asa purely electrical effect, the polarization current causes apolarization of the body, in which electric charges accumulate on theskin, if the latter is dry and the body is substantially insulated fromits surroundings. The polarization charge density on the skin tracks thefluctuations in the applied external field. For an external electricfield that varies as a square wave, the polarization currents flow onlyas brief pulses in response to the edges of the square wave. Thepolarization current pulses then have sharp leading edges, followed byan exponential decay with an e-folding time

    T.sub.c =(ε/ε.sub.o)ε.sub.o η, (1)

where ε_(o) is the permittivity of free space (8.85×10⁻¹² farads/m),ε/ε_(o) the average dielectric constant of the biological tissue, and ηthe average resistivity. T_(c) is called the charge relaxation time.Using the dielectric constant ε/ε_(o) and resistivity η for muscletissue 16, FIG. 3--3!, we find the estimate

    T.sub.c =710 ns.                                           (2)

After each square wave edge, the current flow in the subject's bodybecomes negligibly small after a few times T_(c). For square wave edgesthat are rounded with a rise time considerably larger than T_(c), thepolarization current pulses are broadened to the rise time of the edges.If spatial averages are used for the dielectric constant andresistivity, the charge relaxation time expressed by (1) is a spatialaverage. However, local relaxation times can differ substantially fromthe spatial average; for instance, the relaxation time of membranesranges from 0.7 ms to 24 ms for the cases listed by Katz 17, table 1!.

For external electric fields that vary slowly compared to the chargerelaxation time (2), the polarization keeps up with the field. Theresultant electric field, i.e., the sum of the applied field and thefield due to polarization, is then essentially always perpendicular tothe skin of the subject, and the electric field on the skin isproportional to the surface density of electric polarization in theskin. As will be discussed, experiments have shown that weak externalfield modulation of cutaneous nerves is due to electric polarization ofthe skin.

The polarization currents are subject to the skin effect 19, p. 5-85!,in which the current density falls of exponentially, from the skin intothe body, with e-folding distance

    δ.sub.s =√(η/(πfμ)),                (3)

where f is the frequency of the applied field, μ the permeability, and ηthe resistivity of the body tissue. Calculation of the skin depth δ_(s)for the frequencies involved in the present invention gives values inexcess of 1 m. It follows that the polarization current paths are notrestricted by the skin effect.

The scale of the polarization current densities can be determined fromthe peak polarization current induced in the subject's body by theapplied external field. This peak current can easily be calculated forthe case that the applied electric field varies as a rounded squarewave. The calculation is illustrated here for the field generator ofFIG. 3. Let the resistors 13 and 14 and the potentiometer 12 all havethe same resistance R_(o), and let the potentiometer wiper be set atfraction α of the total resistance R_(o). With a 3 V battery, the outputvoltage of timer 16 at point 15 is 2.5 V. Therefore, timer 6 produces asquare wave with a voltage of V_(o) =2.5 V. A short calculation showsthat the voltage between the two output terminals 11 swings from αV_(o)/3 to -αV_(o) /3, and that the output impedance, in the absence ofoutput capacitor 22, is

    R.sub.out =α(3-2α)R.sub.o /3.                  (4)

Hence, with an output capacitor C_(o), the peak polarization currentthrough the body of the subject is ##EQU1## where C_(eb) is the part ofthe capacitance between the field electrodes calculated from electrodecharges at the end of electric field lines that go to the subject'sbody, and C_(ee) is the remaining part of the capacitance between thefield electrodes. Eq. (5) holds, provided that R_(o) is much larger thanthe impedance of the subject's body, a condition that is satisfied inpractice. The rise time of the external electric field is ##EQU2##provided that T_(f) is much larger than the charge relaxation time (2)of the subject's body. This condition is satisfied in practice, unless αis very small. For the device of FIG. 3, with an output capacitor C_(o)=1000 pf, R_(o) =1 MΩ, α=1, V_(o) =2.5 V, and the electrodeconfiguration of FIG. 1, with the estimates C_(eb) =1 pf, C_(ee) =1 pf,the peak current I_(max) of (5) becomes

    I.sub.max =5.0 nA,                                         (7)

and the rise time T_(f) of (6) is found to be

    T.sub.f =0.33 ms.                                          (8)

Although these results were derived for the generator of FIG. 3, underthe assumption that the timer produces a square wave with sharp edges,they will remain valid for rise times up to 100 ns. Comparison of thepeak polarization current (7) with the 1 mA or so required for classicalnerve stimulation 6,7! shows that the latter does not occur in theexperiments under discussion. Estimating, for the setup of FIG. 1, thearea of the skin that is subjected to appreciable field strengths as2A=600 cm², the peak polarization current density has over this area aspatial average <j>=I_(max) /A, which comes to

    <j>=17 pA/cm.sup.2                                         (9)

Using η=400 Ohm cm as an average tissue resistivity 16, FIG. 3--3!, thespatial average peak internal electric field strength <E_(i) > thataccompanies the average peak current density <j> of (9) is

    <E.sub.i >=6.8 nV/cm,                                      (10)

for the case considered. These results are spatial averages of temporalpeaks. In order to estimate the deviations from the average caused bynonuniformities in conductivity, consider a membrane with surfaceresistivity of 4000 Ohm cm² 17, table 1! subject to the perpendiculardensity (9). The potential difference across the membrane is thenperturbed by a mere 68 nV. Even if a factor 10 is used to account forthe local nonuniformities in current density, the resulting peakmembrane potential perturbation of 680 nV is orders of magnitude belowthe membrane depolarization required for firing. This again shows thatclassical nerve stimulation does not occur. Since the applied field actson the nerves, as evidenced by the observed physiological effects, theaction must be a modulation of the spontaneous firing pattern of thenerve. The question remains whether the modulation is caused by thepolarization currents or by the polarization charges on the skin.

In order to investigate this question, two experiments were performed.The field generator of FIG. 3 was used in both, with a 1000 pf outputcapacitor 22, V_(o) =2.5 V, and R_(o) =1 MΩ, where R_(o) is theresistance of resistors 13 and 14, and potentiometer 12. The fieldelectrodes were aluminum foil rectangles of 8×17 cm, placed over theupper skin of the subject's feet, with 1.5 cm insulation between theskin and the foils. The field electrodes were shielded on the outsidewith 8.5×20 cm rectangular pieces of grounded aluminum foil, separatedfrom the field electrodes by a 0.5 cm thick layer of insulation. Thesubject's feet, fitted with the shielded field electrode assemblies,were placed in a 36×31×53 cm cardboard box, covered on the outside withgrounded aluminum foil; the front opening of the box was shielded by acurtain of grounded insulated strips of aluminum foil. With thisarrangement, the electric field was mainly confined to the 1.5 cm spacebetween each field electrode and the opposing area of skin; any fieldspilling out from this space was essentially kept in the box by thegrounded shield on the outside of the box and by the grounded curtain infront. The capacitance between the field electrodes via the subject'sbody is estimated as C_(eb) =11 pf, using a dielectric constant of 2.6for the styrofoam insulation. The remaining capacitance between thefield electrodes is estimated as C_(ee) =33 pf. With the outputcapacitor C_(o) =1000 pf, V_(o) =2.5 V and R_(o) =1 MΩ, Eq. (5) gives apeak polarization current of I_(max) =53 nA, multiplied by a factor thatranges from 1/3 to 1, as the intensity control potentiometer is advancedfrom small α to α=1. Full ptosis was observed with intensity controlpotentiometer settings from α=1 to α=0.06, at a frequency near 0.53 Hz.

Next, the experiment was repeated with one modification: the upper skinof the subject's feet, in the area opposite the field electrodes, wascovered with a layer of conductive jelly, followed by a thin layer ofoverlapping strips of aluminum foil, and a thin insulating plasticsheet. In this arrangement, the polarization currents in the subject'sbody end up not on the subject's skin opposite the field electrodes, buton the aluminum foil covering of that skin area. The conductive jellybetween skin and aluminum foil assures that the polarization chargesmake their way to the foil without delay beyond the charge relaxationtime T_(c) of (2). As a result, the polarization currents that flow inthe subject 's body are the same as in the previous experiment, butduring the plateaus of the square wave, after a few times T_(c), theskin is not subjected to an electric field. With intensity controlsettings α ranging from 1 down to 0.06, and tuning through the frequencyrange from 0.490 to 0.589 Hz, only very faint and fleeting ptosis wassporadically experienced for very short times; it could not be trackedin the usual manner by slowly tuning to lower frequencies. This resultis to be compared with the full ptosis occurring in the previousexperiment in which the feet were not covered with the highly conductivelayer.

Varying the intensity control settings α in the two experiments gavepairs of settings in which the polarization current densities on theskin in the areas opposite the field electrodes is the same for the twoexperiments. For each of these pairs, the values of α are somewhatdifferent, because the metal covering of the skin used in the secondexperiment extends to border areas for the purpose of capturing the edgefield flux; therefore, the effective area of skin involved in the secondexperiment is slightly larger than in the first experiment. Consideringthe existence of these pairs of α settings for which the polarizationcurrent densities on the skin are the same for the two experiments, andthe essential absence of ptosis in the second experiment, it isconcluded that ptosis is essentially not caused by polarization currentsin the skin. Moreover, settings with the same α give about the samepolarization currents in the rest of the subject's body, away from theskin area opposite the field electrodes. It is therefore concluded thatptosis is essentially not due to stimulation or modulation of nervesother than cutaneous nerves, and it is not due to polarization currentsin the brain either. It also follows that the ptosis is essentially notdue to any stray electric field standing on the scalp or any other partof the skin other than the skin area lying directly across the fieldelectrodes. It is concluded that the ptosis is essentially due toexternal electric field effects other than the polarization current, andthat ptosis occurs essentially through cutaneous sensory nerves.

What are the effects of the external electric field, besides thepolarization current? One such effect is the force exerted by theexternal field on hairs. However, experiments in which the field isexclusively applied to glabrous skin also give ptosis; hence, hairs arenot involved in an essential way. The only possibility remaining is ashallow penetration of the external electric field into the subject'sskin. Two such mechanisms have come to mind.

The first mechanism is due to thermal motion of the ions, that cause asmearing of the polarization charges through a Debye layer at the skinsurface. The scale of such penetration in an electrolyte with monovalentions of opposite charge is given by the Debye length 20! ##EQU3## whereε is the permittivity, e the elementary electric charge, n theconcentration of one of the ion species deep in the electrolyte, andV_(T) =kT/e is the thermal voltage (26 mV at the normal skin temperatureof 34° C.); k is the Boltzmann constant and T the absolute temperature.If the electrolyte is exposed to an external electric field E_(o)perpendicular to its boundary, then at thermodynamic equilibrium thepotential at depth z in the electrolyte is approximately

    V(z)=E.sub.o δ.sub.d e .sup.-/δ.sbsp.d,        (12)

where δ_(d) is the Debye length given by (11), and the voltage is takenwith respect to points deep in the electrolyte. The approximation (12)is good if E_(o) δ_(d) <<V_(T). From (12) one has for the electric field

    E(z)=E.sub.o e.sup.-z/δ.sbsp.d.                      (13)

These results are easily derived from balancing conduction and diffusioncurrents, together with the Poisson equation that relates the potentialto the charge distribution. The calculation can be readily extended tothe case of bivalent ions, and to mixtures of ions with differentvalences.

The above considerations for an electrolyte are applicable to thedermis, because of its considerable fluid content. But one may apply thetheory also to the epidermis. This outer layer of the skin containshorny cells that suppress the mobility of ions. However, the relationbetween mobility and diffusivity of ions is still given by the Einsteinrelation. Therefore, the equilibrium thermodynamics of ions in theepidermis is the same as in an electrolyte. Since the ion concentrationin the epidermis is relatively small, the Debye length is relativelylarge; for example, for an ion density of 10⁷ per cm³ and a dielectricconstant of 4, the Debye length (11) is 0.54 mm. Sensory receptors indermal papilla that protrude into the base of the epidermis are thensubjected to the remnant of the electric field as it penetrates from theoutside, in the manner shown by Eq. (13). If the cytoplasm of thereceptor is at the same potential as the deep body tissue, then themembrane potential at the tip of the receptor is perturbed by the aboutthe voltage (12), using for z the thickness of the epidermis. Taking 0.2mm for that thickness, and parameters of the epidermis as in the aboveexample, an external field of 1 V/m on the skin is found to perturb themembrane potential of the receptor tip by about 0.4 mV.

Such a change in membrane potential is much too small to fire the nerve.However, as pointed out by Terzuolo and Bullock in a classical paper25!, modulation of the frequency of an already active neuron can beachieved with voltages very much lower than those needed for theexcitation of a quiet neuron. Voltage gradients as small as 1 V/m acrossthe soma were sufficient to cause a marked change of firing of adaptivestretch receptors of crayfish. Terzuolo and Bullock further remark thatthe value of the critical voltage gradient for this effect may actuallybe much smaller than 1 V/m. The 0.4 mV membrane voltage perturbationcalculated above for the example may be sufficient to cause frequencymodulation of the firing pattern of the receptors investigated byTerzuolo and Bullock. Perhaps the same behavior occurs for other slowlyadapting mechanoreceptors that exhibit spontaneous firing, such asRuffini endings and Merkel cells, which are found roughly at a depth of0.2 mm in the skin 21-23!.

A second mechanism for penetration of the external field into theepidermis is provided by sweat ducts. These narrow ducts are normallykept at least partially filled by the sweat glands and capillary action.The higly conducting thin sweat column in the duct will be polarized bythe external electric field. As a result the field will be severelydistorted, causing the equipotential surfaces to crowd together near thetips of the columns, and dip deep into the epidermis in between thesweat ducts. As a result, a local field that is a small fraction of theexternal field E_(o) acts on cutaneous receptors which lie in papillathat protrude into the base of the epidermis. The associated potentialmust be added to that due to the first mechanism.

Cold receptors also lie at shallow depths 22! and exhibit spontaneousfiring, so that they need to be considered as candidates for modulationby externally applied weak electric fields. Therefore, an experiment wasperformed in which steady electric fields of up to 1 KV/m were appliedto the skin. If modulation occurs, these electric fields may induce asensation of skin temperature change. No such sensation was experienced.However, there may have been rapid adaption to the electric fieldstimulus, and the effect of the field on the firing pattern of coldreceptors may differ in nature from the pattern change due totemperature. The latter possibility is suggested by the complicatedcoding of temperature information, which is much more intricate thanmere frequency modulation 26!. Therefore, the observed absence of atemperature sensation in steady-state electric field application doesnot quite rule out modulation of cold receptors by the applied externalelectric field.

There have been further developments, as follows.

It has been observed that lower field strengths suffice for theexcitation of sensory resonances when the skin area of dominant fieldapplication is increased. This "bulk" effect is important for the properuse of the invention, and can be understood as follows. The field causesa frequency modulation of the stochastic firing of the affected afferentfibers. If these fibers synapse, either directly or indirectly, upon asumming neuron, then the sequence of current injection spikes into thedendrite of the neuron will be a slightly modulated Poisson stream. Forzero modulation a Poisson distribution is expected on theoreticalgrounds if the number N of synapsing afferents is large, since theafferent spike trains add and interlace. This results in ahigh-frequency sequence of charge injections, in which the features ofthe individual afferent spike trains are substantially washed out, inmuch the same way is density nonuniformities of a substance suspended ina fluid are removed by stirring. The Poisson distribution is found to bea good approximation in computer simulations with N of the order of4000, substantially independent of the details of the firing probabilitydistributions for the individual afferents. As a consequence of thePoisson distribution, the variance as well as the mean of the number ofinjection spikes into the summing neuron that occurs in a fixed timeinterval Δt is

    λ=Nf.sub.o Δt,                                (14)

where f_(o) is the average frequency of the afferent spike train,assumed to be the same in each afferent, for simplicity. For large N theexcitatory synaptic current needs to be balanced with an inhibitorycurrent, lest the integrated signal by far exceeds the firing thresholdand the summing neuron is locked into a maximal firing state. Thebalance requires that, in addition to N excitatory neurons, roughly Ninhibitory neurons also synapse on the summing neuron The inhibitorycurrent spikes contribute to the noise, thus increasing the variance byabout a factor 2. Balanced excitatory and inhibitory activity has beenrecently considered as a mechanism for rendering cortical neuronssensitive to small fluctuations in their synaptic current; see 24! andthe references contained therein. With modulation present, the Poissondistribution still stands short-term, but λ has now a slow sinusoidalvariation with the frequency of the applied electric field. Allmodulated afferents contribute coherently to this sine wave. As aresult, the signal-to-noise ratio of the fm signal that is present inthe temporal density of the current injection spikes is proportional tomNf_(o) /√(2f_(o) N)=m√(f_(o) N/2), where m is the depth of thefrequency modulation. The latter is expected to be proportional to theapplied external field amplitude E. Hence, one expects thesignal-to-noise ratio to be proportional to E√(f_(o) N). The fm signalis somehow demodulated by subsequent neural circuitry. The mattercontains or is followed by nuisance-guarding circuits, with the resultthat the observable response to the field application exhibits aneffective intensity window. One expects the ultimate response to be afunction of the signal-to-noise ratio of the current injections into thesumming neuron, so that

    observable response=function of (E√(f.sub.o N).     (15)

Eq. (15) shows the bulk effect. For excitation of sensory resonancesthrough modulation of cutaneous nerves, N is roughly proportional to theskin area A_(s) over which the field is predominantly applied, and alsoto the surface density p of the affected nerves, so that in (15) one has

    N=cpA.sub.s,                                               (16)

where c is a constant. If the fm detection circuitry receives inputsfrom M similar summing neurons, the results (15) and (16) still hold ifN is replaced by MN. Very shallow frequency modulation can be detectedamidst the large fluctuations occurring in the spontaneous firing of theindividual afferents, if the product MN is large. This result is helpfulin understanding the exquisite sensitivity of the human electroceptionobserved and discussed here. Stochastic resonance 33! perhapscontributes to the sensitivity as well.

The peak value (10) of the internal electric field induced by anexternal field of 1 V/m with rounded square wave time dependence at afrequency near 1/2 Hz shows that the internal field is a very smallfraction of the external field. The same conclusion holds for sinusoidalfields, for which the internal field is easily found to be

    E.sub.i =2πfT.sub.c E.sub.o,                            (17)

where T_(c) is the relaxation time (1), f the field frequency, and E_(o)the external electric field. For f=1/2 Hz, and the value T_(c) given by(2), Eq. (17) gives for the internal electric field

    E.sub.i =2.2×10.sup.-6 E.sub.o.                      (18)

It follows that, for the purpose of calculating the field induced on theskin by field electrodes, the internal electric field may be neglected,so that the subject's skin is an equipotential surface. For theconfiguration of FIG. 2, the skin voltage is then determined by acapacitive voltage divider with two capacitors, one formed by the leftelectrode 2 and the apposing skin area 36', and the other formed by theright electrode 2 and the skin area 36. If both electrodes are placedopposite the skin by a small separation d, the electric field on theskin in the areas 36 and 36' is approximately

    E=V/2d,                                                    (19)

where V is the voltage applied between the field electrodes.

In certain experiments and clinical applications there is a need for anexternal electric field that is strictly confined to two selected skinregions. Such a field can be set up with a shielded electrode pair asdepicted in FIG. 8, where field electrodes 2 and 2' of identical shapeand size are closely apposed, in parallel fashion, respectively byelectrodes 38 and 39 called shield electrodes. The latter have the samesize and shape as the field electrodes 2 and 2', and are positioned andoriented such as to bring their contours in registration with those ofthe corresponding electrodes 2 and 2'. Furthermore, a conductor 40connects the shield electrodes, so that they have the same potential.Electrodes 2 and 2' are connected by wires 41 to the input port 55 whichis to receive a voltage from the generator. With the generator voltageapplied to the input port 55, the voltage on the field electrodes 2 and2' is respectively V₁ and V₂. Although not shown, insulation is appliedbetween electrodes 2 and 38, and between electrodes 2' and 39.Optionally, insulation is applied to the top and bottom of the tworesulting structures as well, resulting in two 5-layer sandwiches. Thelatter are positioned in close proximity of the skin 37 of the subject,in the orientation shown in FIG. 8. If the sandwiches are placedparallel and at equal distances to the skin 37, then both the skin andthe shield electrodes have the potential (V₁ +V₂)/2, so that no fieldlines stand between the shield electrodes 38 or 39 and the subject. Itfollows that the external electric field is then confined to four narrowspaces, viz., the space between electrode 2 and the skin 37, betweenelectrode 2' and the skin, between electrode 2 and the shield electrodes38, and between electrode 2' and shield electrode 39, except for edgefields pouring from the edges of the narrow spaces. These edge fieldsextend over a distance of the order of the electrode separation or thedistance from electrode 2 or 2' to the skin. If these separations arevery small, so will be the spatial extents of the edge fields, and theexternal field on the skin then will be essentially confined to the skinareas directly apposed by the electrodes 2 and 2'. Electrodes 2 and 2'need not be positioned in close proximity to each other.

In the foregoing discussion the field electrodes 2 and 2' were assumedto have the same shape, size, and distance to the skin. One can deviatefrom these conditions by making adjustments in the distances at whichthe shield electrodes are applied over the field electrodes 2 and 2',such as to assure that the shield electrodes are at the same potentialas the skin. The shield electrodes 38 and 39 may be conductive foils orconductive meshes. The conductor 40 may be a conductive foil, which maysimply be the continuation of the shield electrodes 38 and 39. If thefield electrodes 2 and 2' are deployed at a short distance from eachother, the shield electrodes 38 and 39, together with the conductor 40may be implemented as a single conductive foil.

A well-designed and deployed shielded pair of field electrodes limitsthe field application essentially to the skin area directly apposing thefield electrodes. Therefore, the shielded pair can be used on skin areasvery close to the head, without causing substantial polarizationcurrents in the brain. An important example of such deployment islocalized field application to the skin overlying the vagus nerve in theneck.

A new sensory resonance has been found near 2.4 Hz. The resonance showsup as a sharp increase in the time of silently counting backward from100 to 70, as fast as possible, with the eyes closed. The counting isdone with the "silent voice" which involves motor activation of thelarynx appropriate to the numbers to be uttered, but without the passageof air, or movement of mouth muscles. The motor activation causes afeedback in the form of a visceral stress sensation in the larynx.Counting with the silent voice must be distinguished from merelythinking of the numbers, which does not produce a stress sensation, andis not a sensitive detector of the resonance. The larynx stress feedbackconstitutes a visceral input into the brain and thus may influence theamplitude of the resonance. This unwanted influence is kept to a minimumby using the count sparingly in experiment runs. The protocol adapted inour laboratory, after extensive trial and error, is to have experimentruns of 40 minutes duration, with counts taken at times 0, 20, and 40minutes into the run. In early experiments the count was done from 100to 70, but as experience was gained, we switched to the more sensitive100-60 counts. Since counting is a cortical process, the 2.4 Hzresonance is here called a cortical sensory resonance, in distinction tothe autonomic resonance that occurs near 1/2 Hz. In addition toaffecting the silent counting, the 2.4 Hz resonance is expected toinfluence some other cortical processes as well. It was found that inthe long run the resonance has a sleep inducing effect. Very longexposures cause dizziness. The frequency of 2.4 Hz raises concerns aboutkindling; therefore, the general public should not use the 2.4 Hzresonance until this concern has been addressed properly in experiments.

The sensitivity and numerical nature of the silent count makes it a verysuitable detector of sensory resonance, thereby affording severalexperiments which clarify somewhat the processes involved, and provideguidance for the proper use of the invention.

First, the experiment aimed at resolving the question whether it are thepolarization currents or the polarization charges that cause theexcitation of the 1/2 Hz autonomic resonance has been repeated for the2.4 Hz cortical resonance, using the same field strengths applied in thesame manner to the same areas of skin, but with a sine wave instead of arounded square wave. The amplitude of the voltage applied to the fieldelectrodes was 1.45 V, resulting in an external electric field at theskin with a maximum amplitude of 48 V/m. A frequency of 2.407 Hz wasused, and the counts were done from 100 to 60. As for the 1/2 Hzexperiments discussed, the electric field was applied to the dorsum ofthe feet in a localized manner. In the first experiment the silentcounts were 37 s at the start t=0 of the run, 53 s at t=20 minutes, and75 s at t=40 minutes, the end of the run. The pronounced increase ofcounting time shows excitation of the 2.4 Hz resonance. In the secondexperiment the conditions and parameters were the same, except that theskin of the dorsum of the feet was covered with conductive jelly andaluminum foil, all insulated from the field electrodes. This arrangementremoves the polarization charges from the skin, whereas the polarizationcurrents in the skin and the body are the same as before. The countswere 32 s at t=0, 34 s at t=20 minutes, and 33 s at t=40 minutes, sothat the resonance was not excited. Comparison of the two experimentsshows that the excitation of the resonance is not due to polarizationcurrents, but rather to polarization charges on the skin, in agreementwith the conclusion reached above for the 1/2 Hz autonomic resonanceexperiments.

The magnitude of the polarization current densities in the subject iscalculated as follows. With an estimated 11 pf capacitance between thefield electrodes via the subject's body, the polarization currentamplitude comes to 241 pA. Assuming that this current is spread over askin area that is 10% larger than the area of the nearby fieldelectrode, the maximum current density in the subject's body is found tobe 1.6 pA/cm². The experiment shows that such a small current densityapplied to cutaneous nerves in the dorsum of the foot is not capable ofexciting the 2.4 Hz resonance, but the accompanying polarization chargescan.

In the described experiments the polarization current through the skinis concentrated in the skin area S immediately apposing the fieldelectrodes, fanning out from there into deeper lying tissue. A similarcurrent distribution can be set up by means of contact electrodesattached to the skin in the area S. This affords another check on theconclusion that the resonance is not excited by the currents, in theparameter range considered. To perform this check, the output of thesinusoidal voltage generator was connected to the contact electrodes viaa small capacitor which at the low frequencies presents an impedancevery much larger than that of the subject's body. The generator therebybecomes effectively a current source. The two contact electrodes had thesame size and shape as the field electrodes in the field experimentsdescribed above, and each was attached to the dorsum of the foot througha layer of conductive jelly. Passing in this manner a sinusoidal currentwith an amplitude of 48 nA at 2.417 Hz gave rise to a 100-60 count of 35s at t=0, 36 s at t=20 minutes, and 34 s at t=40 minutes, showing thatthe resonance was not excited. The maximum current density in the skinwas 321 pA/cm², considerably larger than in the field applicationdiscussed. Yet, the current did not cause excitation of the 2.4 Hzresonance. It may be remarked that the current density of 321 pA/cm²perhaps falls outside the effective intensity window, but that is notthe case, as follows from the next experiment discussed.

Thus far arrangements have been discussed where the modulation ofafferents by the field occurs in the receptors of afferent fibers. Anessentially different situation of interest occurs when the tissueunderlying the skin area of predominant field application is traversedby a nerve that has no receptors in the skin area. The question thenarises whether the spike trains carried by the afferent fibers in thenerve can be modulated without causing classical nerve stimulation.Since polarization charges on the skin cannot have an effect in thiscase, any modulation occurring must be due to the polarization currents.The origin of the currents does not matter, so that they may as well beintroduced by contact electrodes, since this arrangement affords easiercontrol of the current magnitude for research purposes. An experimentwas done in which currents in the tissue were produced by contactelectrodes (3M red dot™, 22×22 mm) placed on the skin at the back of theright knee, with a center-to-center separation of 45 mm, such as toexpose the underlying sciatic nerve to longitudinal currents. For asinusoidal current with a peak density amplitude of 3.4 nA/cm² at afrequency of 2.410 Hz, the 100-60 counts were 33 s at t=0, 54 s at t=20minutes, and 67 s at t=40 minutes, showing excitation of the 2.4 Hzresonance. The current density of 3.4 nA/cm² is much too small forcausing classical nerve stimulation. No excitation was found for asimilar current injection transverse to the nerve. The experiments showthat indeed, afferent fibers in a nerve can be modulated by electriccurrents without undergoing classical nerve stimulation. The currentdensities at which modulation occurred were a factor 10 larger than inthe previously discussed experiment with the dorsum of the foot, whereinthe 2.4 Hz resonance was not excited. The finding that transversecurrents do not excite the resonance shows that the modulation is reallydone on the afferent fibers, and not on receptors.

Similar results were found for sinusoidal current applications to theskin over the right vagus nerve in the neck. Exposure to longitudinalcurrents in the range from 200 pA/cm² to 60 nA/cm² caused excitation ofthe 2.4 Hz resonance, but transverse currents showed no effect. The factthat the current density of 200 pA/cm² caused excitation of theresonance while 321 pA/cm² applied to the dorsum of the foot wasineffective is understandable as due to the bulk effect discussed above;the afferents are much more numerous in the vagus nerve than in theaffected region in the foot experiment. To get further data on thisissue, we measured the effective intensity window for excitation of the2.4 Hz resonance through vagal modulation with longitudinal currentsapplied by contact electrodes attached to the overlying skin. Thecontact electrodes used were again a pair of 3M red dot™ electrodes withcenters 45 mm apart. To provide longitudinal currents, the electrodeswere placed on the skin of the neck over the right vagus nerve, oneabove the other along the direction of the underlying nerve. The resultsare shown in FIG. 9, where the time needed for the silent count from 100to 70 is plotted versus the amplitude of the total current passedthrough the subject by the contact electrodes placed on the neck. Thecurrent was sinusoidal with frequency of 2.466 Hz. For a fixed currentamplitude, the 100-70 counting time was measured at the beginning, t=0,of the current application, at t-20 minutes into the experiment run, andat t=40 minutes at the end of the run. In FIG. 9 the measured countingtimes are shown as graph 73 for t=0, graph 74 for t=20 minutes, andgraph 75 for t=40 minutes. The effective intensity window is clearlyseen to extend from about 100 pA to about 200 nA. The apparant anomalynear point 74 is attributed to chemical detuning. Dividing by theelectrode area of 484 mm², the window for the peak current density inthe subject is found to range from 21 pA/cm² to 41 nA/cm². These currentdensities are much too small to cause classical nerve stimulation. Thepreviously discussed modulation mechanism involving the Debye layer inthe epidermis does not apply in this case since the modulation does notinvolve receptors, but rather afferent fibers in a nerve that runs inthe tissue underlying the skin region of the current injection. It mustbe that longitudinal electric currents in the tissue surrounding thevagus nerve can affect the propagation velocity of action potentials inthe afferents; fluctuating applied currents would then result infrequency modulation of the spike trains received by the brain. Sincethe propagation velocity of action potentials along an axon isinfluenced by the membrane conductance, and the latter is a sensitivefunction of the membrane potential 29!, the propagation speed can indeedbe modulated by perturbations of the membrane potential brought about bylongitudinal currents superimposed on the currents that accompany theaction potential propagation, considering the nonuniformities ofconductivity in the current path distribution. The modulations ofpropagation speed brought on by the currents are very small, but theycan produce a fm of signals received by the brain that suffices for theexcitation of a sensory resonance, if the frequency of the current ischosen properly. The influencing of the action potential propagationspeed along an axon by an external electric field is of great importanceto neural science and needs to be investigated further.

Further experimentation has shown that sensory resonances can be excitedby external fluctuating electric fields with amplitudes on the skin muchlower than 1 V/m. This was already known from experiments with the 1/2Hz resonance which shows ptosis of the eyelids occurring at fieldamplitudes of 20 mV/m on the skin, using a closely spaced electrode pairplaced some distance from the subject, such as to expose a large area ofskin to the weak field. The discovery of the 2.4 Hz resonance with themore sensitive and quantitative detector in the form of the silent countmade measurements at even lower field strengths possible. In theseexperiments we used a closely spaced pair of rectangular fieldelectrodes measuring 59×44 cm, oriented parallel to the line to thenearest point on the subject's body. The electrodes were driven by asine wave with amplitude of 1.25 V:, at frequency near 2.4 Hz. Theelectrode pair was placed at various distances from the subject, aboutat hip height. The distances were large enough to expose a large skinarea to the field. The maximum field induced on the subject's skin wasestimated from a model wherein the subject is represented as a 24 cmradius conductive sphere. The results for the silent 100-60 count areshown in FIG. 10, where the counting time at the beginning, t=0, of therun, at t=20 minutes, and t=40 minutes is shown respectively by graphs76, 77, and 78. The crossover of graphs 77 and 78 is attributed tochemical detuning. A pronounced slowing of the counting is seen to occuralready at a peak field external field amplitude of 10 mV/m. FIG. 10shows an effective intensity window that extends from about 8 to 190mV/m field amplitude. Using the model mentioned above, the effectiveintensity window was expressed in terms of the polarization current inthe subject's body; the window is found to extend from 0.25 to 5.9 pA.

Since in the experiments the distance s from the center of the electrodepair to the subject's body varied from 64.5 cm to 208 cm, there wasconsiderable variation of the skin area A_(s) of predominant fieldapplication, which in first approximation is proportional to s².Therefore it is of interest to consider the bulk effect discussed above.Using Eqs. (15) and (16), ignoring the effect of the surface density pof cutaneous nerves, and taking √A_(s) as the distance s, the graphs ofFIG. 10 may be replotted in terms of the quantity E_(max) s. The resultis shown in FIG. 11, where the graphs for t=0, 20, and 40 minutes areshown respectively as 79, 80, and 81. The effective intensity window isseen to extend from about 17 to 123 mV, in terms of E_(max) s. That thevoltages are comparable to membrane potentials is deemed fortuitous.

In the above experiment, different field strengths were obtained byputting the electrode pair at different distances s from the subject.This resulted of course in different areas A_(s) of predominant fieldapplication. As a check on the validity of Eq. (15), an experiment wasperformed in which A_(s) is fixed, and the field strength is varied bychanging the voltage applied to the field electrodes. The latter were ashielded pair as in FIG. 8, with field electrodes of 223×230 mm appliedto the thighs of the subject at a distance of 5 mm from the skin. Asinusoidal generator voltage was used with frequency of 2.408 Hz and anamplitude of 1.25 V. Before application to the electrodes, the generatoroutput voltage was reduced by an adjustable voltage divider. Silentcounts from 100 to 60 were done at times t=0, 20, and 40 minutes intothe experiment run. The resulting counting times are plotted as functionof E√A_(s), where A_(s) is the skin area of predominant fieldapplication, which here is equal to the electrode area of 513 cm². E isthe electric field on the skin apposing the field electrode; E isuniform and equal to E_(max) introduced above. The resulting plots areshown in FIG. 12, where 82, 83, and 84 are respectively the countingtime plots for t=0, 20, and 40 minutes. The anomaly at the data pointswith E√A_(s) =79.5 may perhaps be attributed to chemical detuning thatdepresses the counting times, but the matter needs furtherinvestigation. The data reveal an effective intensity window thatextends from 18.2 to 158 mV in terms of E√A_(s). Comparison with FIG. 11shows that the windows for the two experiments are in rather goodagreement, considering the crudeness of the model used, and the neglectof differences in surface density p of cutaneous nerves in the skinareas involved; see Eqs. (15) and (16).

In order to see the effect of surface density p of cutaneous receptors,another experiment was done in which a shielded pair of small fieldelectrodes was applied to the tip of the index and middle fingers of theleft hand. Since the receptor density p is larger on the finger tipsthan on the thighs, the values for E_(max) √A_(s) in the window areexpected to be less than for the thighs experiment. The field electrodearea was 15×20 mm, and both field electrodes were applied at an averagedistance d=0.5 mm from the skin, accounting for the distance variationdue to the ridges on the fingerprint skin. The voltage applied to thefield electrodes (2 and 2' of FIG. 8) was sinusoidal with an amplitudeof 1.15 V, reduced by a resistive divider, so that different fieldelectrode voltages can be applied from run to run. Counting times from100 to 60 are plotted in FIG. 13 versus E_(max) √A_(s). The graphs 85,86, and 87 show respectively the counting times at t=0, 20, and 40minutes into the run. The data reveal an effective intensity window thatextends from 6.6 to 54 mV, in terms of E_(max) √A_(s). The bimodality ofgraphs 86 and 87 does not appear to be due to chemical detuning, andneeds to be investigated further. Comparison with FIG. 12, where thewindow extends from 18.2 to 158 mV, and use of Eqs, (15) and (16), givesfor the surface densities the ratio

    p.sub.f /p.sub.t =2.9,                                     (20)

where p_(f) and p_(t) are respectively the receptor densities of theaffected cutaneous nerves on the finger tips and on the thighs. Theupper window limits have been used in calculating the ratio (20).

The small ratio (20) is surprising, and it may help in identifying whichtype afferents are modulated. There are four different kinds of nerveendings in fingerprint skin: bare intraepidermal terminals,intrapapillary coils, Merkel cells, and Meissner corpuscles 34!. Thelatter have poor low frequency response. The Merkel cells aremechanoreceptors that are innervated by slow-adapting (SA) afferentswith good low frequency response, which makes them candidates forelectric field modulation with the frequencies used. The cells sometimesare found to be most profuse near the entry of sweat ducts into theunderside of the epidermis 34!. Nearby Merkel cells are thus subjectedto a field that is concentrated by the conductive sweat ducts, so thatthey may get modulated. The matter needs further investigation.

It is of interest to compare the ratio of upper to lower limit of thewindows, as it is independent of the receptor density p; this ratio ishere called the span of the window. For FIGS. 11, 12, and 13, the spanis found to be respectively 7.2, 8.7, and 8.2. The good agreement of thespans of the effective intensity windows for the three experiments withdifferent skin areas of predominant field application supports thenotion that the nuisance-guarding circuitry is the same in all threecases. In contrast, the window span is about 2000 in FIG. 9 whichpertains to excitation not by external electric fields, but bylongitudinal currents applied with contact electrodes to the skinoverlying the vagus nerve in the neck. Our comments on this large spanof 2000 are as follows. First, the afferents in the vagus nerve reportvisceral information, whereas the cutaneous nerve signals aresomatosensory. Since the latter are much more prone to nuisance signalscoming from the environment, the nuisance-guarding circuitry involved isexpected to be more sensitive. It is even somewhat surprising that suchactivity is indicated at all for visceral information. Second, ourmodulation of the vagus nerve and cutaneous nerves are of differentnature, as evidenced by the large current densities needed in the formercase. Perhaps the modulation of the propagation speed along theafferents involved is a strongly nonlinear function of the appliedlongitudinal current density.

Although an effective intensity window has been noticed in the 1/2 Hzexperiments, the window has not been measured, mainly because we lackeda sensitive quantitative indicator. Ptosis of the eyelids, the leadingindicator for the 1/2 Hz resonance, is not nearly as suitable a detectoras the 100-60 counting time for the 2.4 Hz resonance. In the absence ofthe full window information, one can still see whether effectiveintensities for the 1/2 Hz resonance fit the 2.4 Hz windows, in terms ofE_(max) √A_(s). For the 1/2 Hz cases we take two experiments with setupsthat have given satisfactory results as sleeping aids. The first ofthese is illustrated by FIG. 1, with the peak external electric fieldamplitude on the skin estimated as 1 V/m. With the area A_(s) ofpredominant field application estimated as 400 cm², the product E_(max)√A_(s) comes to 200 mV. The second experiment involves a closely spacedelectrode pair of 16 cm² area driven by 3 V peak to peak, and placed ata distance s=30 cm from the subject's thighs. Use of the model mentionedabove gives for the maximum electric field on the skin E_(max) =12 mV/m,so that one has E_(max) √A_(s) =4 mV, using √A_(s) =s. The E_(max)√A_(s) values of 200 mV and 4 mV for these 1/2 Hz resonance cases canperhaps be reconciled with the 2.4 Hz resonance window of FIG. 11,considering differences in the density p of affected cutaneous receptorsin the skin areas of predominant field application involved. This resultsupports the notion that the nuisance-guarding circuitry is the same forthe 1/2 Hz and 2.4 Hz resonances. Further experiments are needed tosettle the question.

For a sinusoidal external field the polarization current density in theskin has approximately the amplitude

    j=2πfε.sub.o E.sub.o,                           (21)

where E_(o) is the external field on the skin, f the field frequency,and ε_(o) the permittivity of free space. For the 1/2 Hz experimentdiscussed in regard to Eqs. (4)-(9), the current density amplitude (21)comes to 2.8 fA/cm². This value is of course very much smaller than thepeak current density of 17 pA/cm² given by (9) for the rounded squarewave. It has been observed that, in weak field experiments withcutaneous nerves, sine waves excite the resonance just as well as squarewaves of the same amplitude, rounded or not. This is consistent with ourconclusion that it are the polarization charges that cause themodulation of the cutaneous nerves, not the polarization currents. Sincethe polarization currents constitute a foreign intrusion, sine waves,with their mimimum polarization currents, are to be preferred from aneurological point of view.

Excitation of the 1/2 Hz resonance is possible with large externalelectric fields, up to 10 KV/m, produced by placing insulated fieldelectrodes directly on the skin of the thighs. In this arrangement, asweat layer quickly develops between the skin and the field electrodeinsulation. This highly conductive layer removes the polarizationcharges from the skin so that the mechanism that relies on the Debyesmearing of the polarization charges in the epidermis cannot operate.Therefore, the modulation of cutaneous nerves in this case must be dueto polarization currents. For the rounded square wave used, the peakpolarization current density in the skin apposing the field electrodesis found to have an amplitude of about 100 nA/cm². This current densitylies somewhat outside the window of FIG. 9, which ranges from 21 pA/cm²to 41 nA/cm², in terms of the current density. The discrepancy isbelieved to be due to the difference in the density of afferents for thetwo cases. Since the afferents of the cutaneous nerves in the dermis areoriented roughly perpendicular to the skin surface, the localpolarization current is longitudinal with respect to the afferentfibers, so that one expects the afferents to be subject to modulation bythe currents, at least by virtue of the action potential propagationspeed effect discussed. In addition, the cutaneous receptors may alsorespond to the large polarization currents. The modulation of cutaneousnerves by the large external field of 10 KV/m in the presence of a sweatlayer between skin and field electrode insulation is thereby understoodto about the same extent as the other modulation situations. It isemphasised that the polarization current density of 100 nA/cm² is stillmuch too small to cause classical nerve stimulation.

Frequencies appropriate for the excitation of sensory resonancesdiscussed lie near 1/2 Hz and 2.4 Hz. Additional sensory resonances maybe found, with frequencies up to perhaps 45 Hz.

Strong fields applied to areas of skin overlying nerves may be used formodulating afferent fibers in these nerves, thereby providing a methodfor manipulation of the nervous system via visceral afferents, as in thevagus nerve. The method differs from that of Wernicke et al. 35! andfrom that of Terry et al. 28!, in that it employs field electrodesrather than contact electrodes, so that it is noninvasive, and there isno reliance on classical nerve stimulation, so that current densititessmaller by a factor 50000 suffice. Furthermore, the present inventionuses excitation of sensory resonance. In our experiments, a shieldedpair of insulated field electrodes is placed on or adjacent to the skinsuch that the line connecting their centers is roughly parallel to theunderlying nerve, afferents of which are to be modulated. The fieldstrength needed for the excitation of sensory resonances can becalculated from (21) if the necessary current densities are known. Forthe excitation of the 2.4 Hz resonance through the vagus nerve, thesecurrent densities can be determined from FIG. 9; accounting for theelectrode area of 484 mm², the window extends from 21 pA/cm² to 41nA/cm². Using (21), the corresponding field strengths for a sine waveare found to range from 3.8 KV/m to 7.6 MV/m. A low voltage sine wavegenerator suffices for the production of fields in a low part of thisrange, if the insulated field electrodes are placed directly on theskin. For instance, with insulating tape 0.076 mm thick (3M Scotch™Mailing Tape), a voltage amplitude of 1 V gives a field of 13.2 KV/m.

Strong-field experiments have been conducted on the sciatic nerveunderlying the skin on the back of the knee, using an insulated doubletof 60×42 mm area. With the doublet positioned in the skin fold of thebent knee, and an 162×135 mm insulation sheet provided such that thepolarization currents cannot be shortened by apposing skin of calf andthigh, the sciatic nerve was exposed to longitudinal polarizationcurrents of the order of 50 pA/cm², caused by fields of about 3.7 KV/mset up by a sine wave voltage of 1.13 V amplitude at a frequency of2.414 Hz. The 100 to 60 counting times were 34 s at t=0, 54 s at t=20minutes, and 59 s at T=40 minutes, showing that the 2.4 Hz resonance wasexcited.

A similar experiment was done in the right armpit, exposing the ulnarnerve to longitudinal polarization currents that were caused by the60×42 mm doublet imbedded in the 162×135 mm insulation sheet discussedabove, using the same voltage amplitude and frequency as before. The100-60 counting times were 33 s at t=0, 57 s at t=20 minutes, and 57 sat t=40 minutes, showing excitation of the 2.4 Hz resonance.

Finally, a strong-field experiment was done on the right vagus nerve inthe neck, using a shielded pair of field electrodes of 22×22 mm area, ata center-to-center distance of 45 mm, oriented such as to expose thenerve to longitudinal polarization currents. The field electrodes weredriven by a sinusoidal voltage with an amplitude of 1.13 V and afrequency of 2.414 Hz. The 100-60 counting times were 34 s at t=0, 68 sat t=20 minutes, and 74 s at t=40 minutes, showing excitation of the 2.4Hz resonance. In spite of the rather close proximity of the skin area ofpredominant field application, the brain was not subjected tosubstantial polarization current densities, by virtue of the strictfield localization by the shielded field electrode pair.

The experiments discussed show that there are two regimes of afferentsmodulation by an electric field applied to a selected skin area. Thefirst regime involves modulation of cutaneous sensory receptors bypolarization charges in the skin, and is therefore called chargemodulation. In the second regime the polarization currents are strongenough to cause modulation of the propagation speed of action potentialsalong axons exposed to the currents, so that the regime is calledcurrent modulation. In both regimes, the polarization currents are muchtoo weak to cause classical nerve stimulation. Sensory resonances can beexcited in both regimes, but the effective intensity windows havedifferent spans. In the charge modulation regime, the window extendsroughly from 20 mV to 140 mV in the parameter E_(max) √A_(s), to beadjusted for different densities of the affected cutaneous receptors. Inthe current modulation regime, the effective intensity window extendsroughly from 21 pA/cm² to 41 nA/cm², to be adjusted for the number ofaffected afferents in the nerve exposed to the polarization currents.The span of about 2000 for this window compared to about 8 for thecharge modulation regime shows that different mechanisms operate in thetwo regimes. Current modulation is suitable for manipulation of thenervous system through visceral or somatosensory afferents in largenerves that are, at places, capacitively accessible through the skin,such as vagus and sciatic nerves. In these cases, the application ofexternal fields can be done with a shielded pair of field electrodes,placed on the overlying skin in the direction of the nerve. When usedproperly, the shielded electrode pair assures that the field is appliedstrictly to the underlying skin, without exposing more distant regionsof the body, such as the brain, to substantial polarization currents.The field strengths appropriate for exitation of sensory resonances inthe two regimes differ by a large factor; for charge modulation, typicalfields on large skin areas range from 10 to 200 mV/m, whereas for thecurrent modulation the fields, naturally for localized small skin areaexposure, are of the order of kilovolts per meter. For both regimes, theproper fields can be produced by the same low-voltage generator, simplyby using different field electrodes and deployment. The doublet placedsome distance from the subject is particularly suitable for chargemodulation of cutaneous receptors over large skin areas, whereas theshielded pair is the field electrode configuration of choice in thecurrent modulation regime, although a single small electrode pair may beused for the special case where it can be completely surrounded by thesubject's skin.

The method is expected to be effective also on certain animals, andapplications to animal control are therefore envisioned. The nervoussystem of mammals is similar to that of humans, so that sensoryresonances are expected to exist, albeit with somewhat differentfrequencies. Accordingly, in the present invention, subjects aremammals.

The invention is not limited by the embodiments shown in the drawingsand described in the specification, which are given by way of exampleand not of limitation, but only in accordance with the scope of theappended claims.

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I claim:
 1. Apparatus for modulating cutaneous nerves in areas ofsparsely innervated skin away from the head of the subject,comprising:field-applying means for applying, predominantly to the saidareas of the skin, an external periodic electric field with a frequencyin the range 0.1 to 2 Hz and such that, over the said areas, the fieldamplitude is between 1 and 25 V/m, for modulating cutaneous nerves inthe said areas of the skin without causing classical stimulation ofcutaneous nerves; and frequency tuning means for tuning the frequency ofthe field-applying means.
 2. Apparatus according to claim 1, in whichthe said field-applying means comprises field electrode means, generatormeans for generating a periodic voltage, and conductor means forconnecting said generator means to said field electrode means, furtherincluding:switching means for interrupting polarization currents throughthe said conductor means, caused by a 60 Hz house field when theapparatus is inactive.
 3. In electrical apparatus for inducing at leastone of a plurality of results, namely relaxation, sleep, and sexualexcitement, and control of tremors, seizures, and panic attacks,comprising:generator means for generating a periodic voltage with apeak-to-peak variation less than 10 V and a frequency in the range 0.1to 2 Hz; field electrode means, electrically connected to the generatormeans, for applying, predominantly to areas of sparsely innervated skinaway from the head of a subject an external periodic electric field,with an amplitude over the said areas between 1 and 25 V/m, formodulating cutaneous nerves in the said areas without causing classicalstimulation of cutaneous nerves; and frequency-tuning means for tuningthe frequency of the generator means.
 4. In an apparatus according toclaim 3, and wherein the field electrode means comprise one fieldelectrode to be placed adjacent to skin area on the hips, buttocks, andlower back of the subject, and another field electrode to be placedadjacent to the skin area on the back side of the thighs and knees ofthe subject.
 5. Apparatus for manipulating the nervous system of asubject, comprising:generator means for generating a periodic voltagewith a peak-to-peak variation less than 16 V, and a frequency less than45 Hz; and field electrode means, electrically connected to thegenerator means, for inducing an electric field on the skin of thesubject to modulate afferent nerves, without causing classical nervestimulation, and without causing substantial polarization currentdensities in the brain of the subject.
 6. Apparatus for manipulating thenervous system of a subject, comprising:generator means for generating aperiodic voltage with a frequency less than 45 Hz and a peak-to-peakvariation less than 16 V; at least two field electrodes, connected tothe generator means, for producing an electric field; one casing forcontaining the generator means and the field electrodes.
 7. A method formanipulating the nervous system of a subject, comprising:selecting, onthe subject, a skin area away from the head; generating a periodicvoltage with frequency less than 45 Hz, and a peak-to-peak variationless than 16 V; applying the periodic voltage to field electrodes forproducing an electric field; and administering the electric fieldpredominantly to said skin area, for modulating afferent nerves withoutcausing classical nerve stimulation, and without causing substantialpolarization current densities in the brain of the subject.
 8. Themethod of claim 7 for exciting in the subject a sensory resonance with aresonance frequency below 45 Hz, further including the step of settingthe voltage frequency to the resonance frequency.